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Regulation and Function of Hox gene lin-39 in C elegans

线虫Hox基因lin-39的调控与功能

基本信息

批准号：
7163472
负责人：
David Eisenmann
金额：
$ 23.7万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE COUNTY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7163472
关键词：
Address Adopted Adoption Adult Amino Acid Sequence Animals Anterior Behavior Binding Binding Sites Biological Models Body Regions Caenorhabditis elegans Caenorhabditis elegans Proteins Cell Fate Control Cells Class Comb animal structure Complex Consensus DNA DNA Binding DNA Microarray Chip DNA Microarray format Defect Development Docking Drosophila genus Gene Expression Gene Targeting Genes Genetic Transcription Genomics Goals Homeodomain Proteins Homologous Gene Homologous Protein Human In Vitro Lead Learning Life Methods Mitogen-Activated Protein Kinases Organism Pathway interactions Pattern Peptide Sequence Determination Phosphorylation Phosphorylation Site Protein Overexpression Proteins RNA Interference Ras Signaling Pathway Regulation Reporter Signal Pathway Signal Transduction Site Structure Tin Vulva base functional genomics homeodomain in vitro Assay in vivo member mutant precursor cell protein function research study sex

项目摘要

The C. elegans Hox gene lin-39 encodes a homeodomain-containing protein similar to the Drosophila Deformed and Sex Combs Reduced proteins, lin-39 is expressed in the C. elegans mid-body region, including the vulval precursor cells, and is required for the proper fate determination of these cells. In these vulval precursor cells, the tin-39 gone is coordinately regulated by both Wnt and Ras signaling pathways. We propose that the Hox gene lin-39 in C. elegans functions as a transcriptional regulator that controls the expression of a set of downstream genes in order to control the fates of the vulval precursor cells. We propose experiments to 1) determine how the Wnt and Ras pathways regulate LIN-39 protein levels, 2) identify LIN-39 binding sites in vitro and assay their relevance in vivo, 3) determine whether phosphorylation alters the functions of LIN-39 in vitro or in vivo, and 4) identify and characterize target genes regulated by L1N-39 using a microarray -based approach. Hox proteins such as LIN-39 are known to function in the patterning of cells along the anterior-posterior axis during the development of all metazoans, and defects in Hox gone expression can lead to drastic defects in development. Although Hox proteins have been characterized in many species, only a handful of target genes have been identified for these proteins. Therefore much can be learned about the function of this important class of master developmental control genes in all organisms, including humans, by the characterization of Hox protein targets in the model system C. elegans, for which full genomic sequence is available and functional genomic approaches are available.

梭线虫Hox基因lin-39编码一种含有同源结构域的蛋白质，果蝇畸形和性梳减少蛋白lin-39在C. elegans 中间体区域，包括外阴前体细胞，并且是正确命运所必需的确定这些细胞。在这些外阴前体细胞中，锡-39协同作用，受Wnt和Ras信号通路的调节。我们认为，Hox基因lin-39在 C.线虫作为一种转录调节因子，控制一组下游基因，以控制外阴前体细胞的命运。我们提出实验1）确定Wnt和Ras途径如何调节LIN-39蛋白水平， 2)在体外鉴定LIN-39结合位点并在体内测定它们的相关性，3）确定是否磷酸化在体外或体内改变LIN-39的功能，以及4）鉴定和表征使用基于微阵列的方法检测L1 N-39调控的靶基因。已知Hox蛋白如LIN-39在细胞沿着所有后生动物发育过程中的前后轴，以及Hox gone表达的缺陷会导致发育的严重缺陷尽管Hox蛋白在许多人中已经被表征，物种，只有少数靶基因已确定这些蛋白质。因此，了解这类重要的主发育控制基因的功能，生物体，包括人类，通过表征模型系统中的Hox蛋白靶点， C. elegans，其全基因组序列是可用的，功能基因组方法是可用的。